JP7452831B2 - Low toxicity human body cleaning agents and low toxicity human body cleaning liquids - Google Patents

Description

The present invention relates to a low-toxicity human body cleansing agent, and more specifically, a low-toxicity human body cleansing agent containing a surfactant with low cytotoxicity as a main component, and a hair wash, etc. containing this cleaning agent as a main component in the blended ingredients. The present invention relates to a low-toxicity cleaning liquid for the human body, such as a shampoo, which can significantly reduce skin disorders associated with skin irritation.

In recent years, a wide variety of detergents have been used to keep the human body and the environment clean. Regarding the human body, shampoos, body soaps, facial soaps, cleansers, etc. are used on a daily basis. The main ingredients of these detergents are surfactants.

On the other hand, skin toxicity or health damage caused by surfactants has been pointed out for a long time (Non-Patent Document 1). It is also known that surfactants easily enter the body through the skin and cause various cytotoxicity and skin diseases (Non-Patent Document 1). It is also known that excessive use of shampoo (hair wash) causes thinning hair and hair loss. This is because surfactants enter the hair follicles on the scalp and damage hair root cells. In particular, for consumers with atopic dermatitis, drug hypersensitivity, or allergic dermatitis, conventional shampoos can be a powerful poison.

As described above, conventional hair washes have not sufficiently considered cytotoxicity to skin cells. Furthermore, there was no data quantifying the cytotoxicity of surfactant components that make up shampoos.

Sakae Sakashita (author) Synthetic Detergent Horrifying Biological Experiments (Genki Health Books) Hardcover-1991/12 Marinovich M1, Viviani B, Galli CL. PMID: 20692893 The predominant role of surfactants in the modulation of toxicity of detergent products: An in vitro analysis of shampoos. Toxicol In Vitro. 1994 Feb;8(1):91-8. Merrick P1, Nieminen AL, Harper RA, Herman B, Lemasters JJ. Cytotoxicity screening of surfactant-based shampoos using a multiwell fluorescence scanner: Correlation with Draize eye scores. Toxicol In Vitro. 1992 Nov;6(6):543-7. Isaksson M1, Jansson L. Contact allergy to Tween 80 in an inhalation suspension. Contact Dermatitis. 2002 Nov;47(5):312-3. Bennike NH1, Johansen JD1. Sorbitan sesquioleate; a rare cause of contact allergy in consecutively patch tested dermatitispatients. Contact Dermatitis. 2016 Apr;74(4):242-5. doi: 10.1111/cod.12536. Epub 2016 Jan 25.

The present invention aims to discover a new surfactant with low cytotoxicity, develop a low-toxic human body cleansing agent with low cytotoxicity using the surfactant, and further develop a low-cytotoxic human body cleansing agent with low cytotoxicity. In addition, we quantified the cytotoxicity of the surfactant components that make up conventional shampoos, and compared them with the surfactants of the present invention. The purpose of this research is to demonstrate that the cytotoxicity of the active agent and shampoo using it is low.

According to the present invention, the following low-toxicity human body cleansing agent and low-toxicity human body cleansing (shampoo, body soap, facial soap, cleansing) are provided.
[1] A low-toxic human body cleansing agent containing a surfactant as a cleaning component, the surfactant comprising:
A polyoxyethylene sorbitol fatty acid ester represented by the following structural formula (1),
A mixture with polyoxyethylene sorbitan fatty acid ester represented by the following structural formula (2) (including cases where the content of polyoxyethylene sorbitan fatty acid ester is 0 % by mass ) as the main component of the surfactant. It contains 50% by mass or more,
The surfactant has an ID50 (a concentration that kills 50% of cells in 30 minutes) of 10,000 μg /mL or more, and the human body cleansing agent has an ID50 of 10,000 μg/mL or more , and is aqueous and has low toxicity. A low toxicity human body cleansing agent characterized by being used as a hair cleansing agent.


(1) In the formula, at least one of the six X groups is a COR _x group, the remaining X groups are hydrogen, and R _x in the COR _x group is a saturated fatty acid group having 4 to 30 carbon atoms, or a carbon It has 16 to 24 unsaturated fatty acid groups.
Further, the average of the total number of ethylene oxide groups (a+b+c+d+e+f) condensed to sorbitol is within the range of 10 to 150.


(2) In the formula, any one of R ₁ , R ₂ , and R ₃ is a saturated fatty acid group having 4 to 30 carbon atoms or an unsaturated fatty acid group having 16 to 24 carbon atoms, and the remaining two are hydrogen. , or a saturated fatty acid group having 4 to 30 carbon atoms, or an unsaturated fatty acid group having 16 to 24 carbon atoms. Further, the average of the total number of ethylene oxide groups (x+y+z+w) condensed to the sorbitan fatty acid ester is within the range of 10 to 150.
[2] The polyoxyethylene sorbitol fatty acid ester has a total average of 10 to 150 tetraoleate sorbes ((a+b+c+d+e+f), any four of the six X groups are oleic acid groups, and the remaining The low toxicity human body cleansing agent according to 1 above, wherein two of the above are hydrogen.
[3] The polyoxyethylene sorbitan fatty acid ester is polyoxyethylene sorbitan monolaurate (polysorbate 20: R ₁ = lauric acid, R ₂ = H, R ₃ = H),
Polyoxyethylene sorbitan monostearate (polysorbate 60: R ₁ = stearic acid, R ₂ = H, R ₃ = H),
Polyoxyethylene sorbitan tristearate (polysorbate 65: R ₁ = R ₂ = R ₃ = stearic acid or palmitic acid),
The above 1 or 2 is characterized in that it is polyoxyethylene sorbitan oleate (polysorbate 80: R ₁ = oleic acid, R ₂ = H, R ₃ = H) or a mixture of these polysorbates. Low toxicity human body cleaning agent as described.
[4] An aqueous low-toxicity human body cleansing liquid containing the low-toxicity human body cleansing agent according to any one of 1 to 3 above as a blended component, which is a polyoxyethylene derived from the low-toxicity human body cleansing agent. The content of the mixture of sorbitol fatty acid ester and polyoxyethylene sorbitan fatty acid ester (including cases where the content of polyoxyethylene sorbitan fatty acid ester is 0 % by mass ) is 0.1 to 80% as a dry solid content. % by mass, the ID50 of the low toxicity human body cleaning liquid is 10000 μg/mL or more, and the low toxicity human body cleaning liquid is used as an aqueous low toxicity shampoo.
[5] The low-toxicity human body cleaning liquid according to item 4 or 5 above, which contains at least one of an anionic surfactant, a cationic surfactant, a nonionic surfactant, or an amphoteric surfactant as an auxiliary cleaning component. .
[6] The auxiliary cleaning component is one or more components selected from Na lauroyl aspartate, Na dilauroyl glutamate lysine, cocamidopropyl betaine, cocamide DEA, and Na surfactin. Low toxicity human body cleaning liquid as described.
[7] The low toxicity human body cleaning liquid according to item 5 or 6 above, wherein the total content of the auxiliary cleaning components is 0.1 to 10% by mass as dry solid content.
[8] The hair according to any of the above items 4 to 7, which contains at least one of a hair moisturizing ingredient, a hair treatment ingredient, a hair nourishing ingredient, a scalp moisturizing ingredient, and a scalp nourishing ingredient in a total of 0.1 to 90% by mass as dry solid content. The low-toxicity cleaning liquid for human body according to any one of the above.

The low toxicity human body cleansing agent of the present invention has significantly reduced cytotoxicity. By continuing to use low-toxicity human body cleansing liquids such as shampoos containing these low-toxicity human body cleansing agents, damage to hair root cells and scalp cells caused by the components of shampoos, etc. can be minimized, and damage caused by shampoos etc. It can be expected to have a hair removal effect and reduce skin disorders. Low-toxicity body cleansers have a cleaning ability comparable to that of conventional shampoos.
The shampoo can also contain treatment ingredients with low cytotoxicity and herbs that promote proliferation of scalp cells. As a result, the low-toxicity human body cleansing agent of the present invention not only has cleaning effects such as the effect on the hair and scalp, but also has the effect of improving the firmness and stiffness of the hair, and the effect of imparting humidity and a moist feeling to the hair.

FIG. 3 is a diagram showing the effect of sorbes on inhibiting cell proliferation. FIG. 2 is a diagram showing the effect of polysorbates on inhibiting cell proliferation. FIG. 2 is a diagram showing the effect of a mixture (50/50) of sorbes and polysorbates on cell proliferation. FIG. 3 is a diagram showing the effect of commercially available shampoos on inhibiting cell proliferation. It is a figure showing an outline of a detergency test.

Hereinafter, the low toxicity human body cleansing agent of the present invention will be explained in detail.
The low toxicity human body cleaning agent of the present invention contains a surfactant as a cleaning component, and the surfactant is a mixture of <1> polyoxyethylene sorbitol fatty acid ester and <2> polyoxyethylene sorbitan fatty acid ester ( However, <2> includes cases where the content of polyoxyethylene sorbitan fatty acid ester is 0).
Here, "<2> Including cases where the polyoxyethylene ether content of the sorbitan fatty acid ester is 0" means that the surfactant contains only the <1> polyoxyethylene sorbitol fatty acid ester as a main component. Say something.

Therefore, the low toxicity human body cleansing agent of the present invention includes <1> polyoxyethylene sorbitol fatty acid ester only as the main component of the surfactant (first embodiment); When the surfactant contains a mixture of sorbitol fatty acid ester and <2> polyoxyethylene sorbitan fatty acid ester (excluding cases where the content of polyoxyethylene sorbitan fatty acid ester is 0) as the main component. There is a (second aspect).

As described above, the main component of the surfactant has a first aspect and a second aspect.
In the first embodiment, the main component of the surfactant is <1> polyoxyethylene sorbitol fatty acid ester .
In the second embodiment, the main component of the surfactant is a mixture of <1> polyoxyethylene sorbitol fatty acid ester and <2> polyoxyethylene sorbitan fatty acid ester.

Next, the low toxicity human body cleansing agent of the first aspect will be explained.
In the first embodiment of the low toxicity human body cleansing agent, the main component of the surfactant is <1> polyoxyethylene sorbitol fatty acid ester .
The <1> polyoxyethylene sorbitol is represented by the following structural formula (1), and an ether is formed by the condensation reaction of all the hydroxyl groups of sorbitol and polyethylene glycol, and further, the terminal hydroxyl group of the polyethylene oxide of the ether and the fatty acid are formed. A polyvalent ester is formed by a condensation reaction with a carboxyl group. However, the polyvalent ester includes a monovalent ester obtained by a condensation reaction between one hydroxyl group at the end of polyethylene oxide and one carboxyl group of a fatty acid.

As shown in the following structural formula (1), polyoxyethylene sorbitol fatty acid ester has a unique structure compared to other surfactants (linear structure). As described below, it is presumed that this structure makes the polyvalent ester a low-toxicity surfactant.
In this specification, various polyvalent esters obtained from polyoxyethylene sorbitol and fatty acids are also collectively referred to as sorbes.

(1) In the formula, at least one of the six X groups is a COR _x group, the remaining X groups are hydrogen, and R _x in the COR x group is a saturated fatty acid group having 4 to 30 carbon atoms, or a carbon number It has 16 to 24 unsaturated fatty acid groups.
Further, the average total of the ethylene oxide groups condensed to sorbitol (a+b+c+d+e+f) is within the range of 10 to 150.

In the six X groups mentioned above, at least one of the six X groups is a COR _x group, and the remaining X groups are hydrogen. Here, two of the six X groups can be COR _x groups, can be three, can be four, can be five, and of the six All can also be COR _x groups.
Note that if the number of COR _x groups is too small, the desired low cytotoxicity effect may not be obtained. On the other hand, if the amount is too large, the surfactant effect may be lowered and the detergency may be lowered.

Specific examples of the saturated fatty acids having 4 to 30 carbon atoms include butyric acid (4 carbon atoms), valeric acid (5 carbon atoms), caproic acid (6 carbon atoms), enanthic acid (7 carbon atoms), and caprylic acid. (8 carbons), pelargonic acid (9 carbons), caprylic acid (10 carbons), capric acid (10 carbons), lauric acid (12 carbons), tridecylic acid (13 carbons), myristic acid (carbon 14), pentadecyl acid (15 carbon atoms), palmitic acid (16 carbon atoms), margaric acid (17 carbon atoms), stearic acid (18 carbon atoms), nonadecylic acid (19 carbon atoms), arachidic acid (20 carbon atoms) ), henicosylic acid (21 carbon atoms), behenic acid (22 carbon atoms), tricosylic acid (23 carbon atoms), lignoceric acid (24 carbon atoms), cerotic acid (26 carbon atoms), montanic acid (28 carbon atoms), Examples include melisic acid (30 carbon atoms).

Specific examples of the unsaturated fatty acids having 16 to 24 carbon atoms include palmitoleic acid (16 carbon atoms), sapienoic acid (16 carbon atoms), α-linolenic acid (18 carbon atoms), and stearidonic acid (18 carbon atoms). ), linoleic acid (18 carbon atoms), γ-linolenic acid (18 carbon atoms), oleic acid (18 carbon atoms), vaccenic acid (18 carbon atoms), linoleic acid (18 carbon atoms), elaidic acid (18 carbon atoms) ), eleostearic acid (18 carbon atoms), eicosapentaenoic acid (20 carbon atoms), dihomo-γ-linolenic acid (20 carbon atoms), arachidonic acid (20 carbon atoms), eicosadienoic acid (20 carbon atoms), mead Acid (20 carbon atoms), Paulic acid (20 carbon atoms), Docosahexaenoic acid (22 carbon atoms), Docosapentaenoic acid (22 carbon atoms), Docosahexaenoic acid (22 carbon atoms), Erucic acid (22 carbon atoms), Tricosyl Examples include acid (carbon number 23), nervonic acid (carbon number 24), and the like.

As mentioned above, the average sum of the ethylene oxide groups (a+b+c+d+e+f) condensed to sorbitol is within the range of 10 to 150. The lower limit of the total average is preferably 20, more preferably 25. The upper limit of the total is preferably 100, preferably 80, and more preferably 60.
If the average of the sum is too small, there is a risk that a low cytotoxic effect may not be obtained. If the average of the total is too large, the surfactant effect may be reduced and the detergency may be reduced.

As explained above, <1> polyoxyethylene sorbitol fatty acid ester has a unique structure compared to other surfactants (linear structure). As will be described later, it is presumed that this structure makes polyoxyethylene sorbitol a low-toxicity surfactant.

Among the above-mentioned polyoxyethylene sorbitol fatty acid esters , the average total of tetraoleate sorbes ((a+b+c+d+e+f) is 10 to 150, any four of the six X groups are oleic acid groups, and the remaining two are hydrogen) is preferred. In addition, in this specification, sorbes tetraoleate in which the average of the sum of a+b+c+d+e+f is about 30 is also referred to as sorbes 30, and sorbes tetraoleate in which the average of the sum is about 40 is also referred to as sorbes 40, and the average of the sum is about 40. Sorbeth 60 tetraoleate is also called Sorbeth 60. The reason why the total is expressed as "about" is that the condensation reaction cannot be strictly controlled during production, and is thought to vary within a range of ±5.

Also, tetraisostearic acid sorbes (the average of the sum of a + b + c + d + e + f is 10 to 150, any four of the six X groups are isostearic acid groups, and the remaining two are hydrogen without being esterified) is also preferable,
Triisostearate sorbes (the average of the sum of a + b + c + d + e + f is 10 to 150, any three of the six X groups are isostearic acid groups, and the remaining three are hydrogen without being esterified) is also preferred .

The sorbes used in the first aspect of the present invention are preferably any of the above-mentioned sorbes tetraoleate, sorbes tetraisostearate, sorbes triisostearate, or a mixture thereof. Moreover, among these sorbes, tetraoleate sorbes are more preferable because they are easy to produce and easily available.

Next, a second embodiment of the low toxicity human body cleansing agent of the present invention will be explained.
In the second embodiment, the main component of the surfactant is a mixture of <1> polyoxyethylene sorbitol fatty acid ester and <2> polyoxyethylene ether of sorbitan fatty acid ester.
The <1> polyoxyethylene sorbitol fatty acid ester is the same as that used in the first embodiment.

The <2> polyoxyethylene ether of sorbitan fatty acid ester has a structure in which a total of about 10 to 150 molecules of ethylene oxide are condensed to sorbitan fatty acid ester, and is represented by the following structural formula (2).
In this specification, polyoxyethylene ethers of various sorbitan fatty acid esters are also collectively referred to as polysorbates.

As can be seen from the structural formula below, polysorbates have a structure in which polyoxyethylene groups are bonded to four OH groups of sorbitol, and fatty acids are bonded to one to three of the OH groups. Polyoxyethylene ether, a sorbitan fatty acid ester, has a unique structure compared to other surfactants (linear structure).

(2) In the formula, any one of R ₁ , R ₂ , and R ₃ is a saturated fatty acid group having 4 to 30 carbon atoms or an unsaturated fatty acid group having 16 to 24 carbon atoms, and the remaining two are hydrogen. , or a saturated fatty acid group having 4 to 30 carbon atoms, or an unsaturated fatty acid group having 16 to 24 carbon atoms. Further, the average of the total number of ethylene oxide groups (x+y+z+w) condensed to the sorbitan fatty acid ester is within the range of 10 to 150.

Examples of the saturated fatty acid having 4 to 30 carbon atoms and the unsaturated fatty acid having 16 to 24 carbon atoms include those similar to the sorbes.

The average of the total number of ethylene oxide groups (x+y+z+w) condensed to the sorbitan fatty acid ester can be set in the range of 10 to 150. If the average of the sum (x+y+z+w) is too small, the desired low cytotoxicity effect may not be obtained. From this point of view, the lower limit of the total average is preferably 15, more preferably 17.
On the other hand, if the average of the totals is too large, there is a risk that the cleaning performance will be reduced. From this viewpoint, the average upper limit of the total is preferably 130, more preferably 100, 80, or 60, still more preferably 50, 40, or 30, and particularly preferably 25.

Preferred specific examples of polysorbates include the following four types <1> to <4>, which differ in the types of fatty acid residues bound.
<1> Polyoxyethylene sorbitan monolaurate (polysorbate 20: R ₁ = lauric acid, CR ₂ = H, CR ₃ = H)
<2> Polyoxyethylene sorbitan monostearate (polysorbate 60: R ₁ = stearic acid, R ₂ = H, R ₃ = H)
<3> Polyoxyethylene sorbitan tristearate (polysorbate 65: R ₁ = stearic acid, R ₂ = stearic acid, R ₃ = stearic acid), polysorbate 65 contains palmitic acid and other fatty acids in addition to stearic acid. There is.
<4> Polyoxyethylene sorbitan oleate (polysorbate 80: R ₁ = oleic acid, R ₂ = H, R ₃ = H)
In these polysorbates, the average of the sum (x+y+y+w) is preferably 20, in which case the sum (x+y+y+w) varies in the range of 10 to 30, preferably 15 It varies in the range of ~25.
Note that the reason why the total number of ethylene oxide groups (x+y+z+w) varies is that the condensation reaction of ethylene oxide cannot be strictly controlled.

The polysorbates used in the second embodiment of the low toxicity human body cleansing agent are preferably polysorbate 20, polysorbate 60, polysorbate 65, polysorbate 80, or a mixture thereof. Further, among polysorbates, polyoxyethylene sorbitan monooleate (polysorbate 80) having one oleic acid bonded thereto is preferred because it has the lowest toxicity. Polyoxyethylene sorbitan monostearate (polysorbate 60) with one stearic acid bonded is the next most preferred, and monolauric acid with one lauric acid bonded is polyoxyethylene sorbitan (polysorbate 20), compared to polysorbate 80 and polysorbate 60. and highly toxic.

In this specification, the main component of the surfactant specifically refers to the component that is contained in the surfactant in an amount of 40% by weight or more and has the largest content, preferably 50% by weight or more, The content is 60% by mass or more, more preferably 70% by mass or more, even more preferably 80% by mass or more, particularly preferably 90% by mass or more.

In addition, in the mixture constituting the low toxicity human body cleansing agent of the second embodiment, the weight ratio of sorbes and polysorbates can be within the range of 3:97 to 97:3, and further, 5: It can be 95-95:5, 10:90-90:10, 20:80-80:20, 30:70-70:30, 40:60-60:40.

The human body cleansing agent of the present invention is characterized by low toxicity. Specifically, ID50 (concentration that kills 50% of cells in 30 minutes treatment) is 2000 μg/mL or more, preferably 3000 μg/mL or more, more preferably 4000 μg/mL or more, and still more preferably 5000 μg. /mL or more, particularly preferably 10,000 μg/mL or more.

The present inventors investigated the cytotoxicity, specifically the ID50, of various surfactants when developing a low toxicity human body cleansing agent. Next, the details of the survey will be explained in detail.

The cytotoxicity of various surfactants was systematically investigated using normal human fibroblast cells. In addition to the above-mentioned sorbes and polysorbates, a wide range of surfactants were selected from ingredients commonly used in commercially available shampoos and ingredients with different structures.

Cytotoxicity was investigated as follows. For sorbes and a mixture of sorbes (sorbes 40) and polysorbates (polysorbate 60), they were added to the cells for 30 minutes at a concentration of 0, 1000, 2000, 5000, 10000, 20000, 50000 μg/mL, and for polysorbates were added to the cells for 30 min at concentrations of 0, 1000, 2000, 5000, 10000, 20000 μg/mL; for other surfactants, concentrations of 0, 100, 200, 500, 1000, 2000, 5000 μg/mL was added to the cells for 30 minutes. After washing away the sorbes, polysorbates, and other surfactants, the cells were cultured for one week. Next, the cells were stained with blue dye and photographed. The results are shown in Figure 1 for the sorbes, Figure 2 for the polysorbates, Figure 3 for the mixture of sorbes (Sorbes 40) and polysorbates (Polysorbate 60), and Figure 3 for the surfactants that make up commercially available shampoos. is shown in Figure 4. Table 1 shows the results of calculating ID50 based on FIGS. 1, 2, 3, 4, etc.

As a result of the investigation, it was found that the cytotoxicity of sorbes and polysorbates is significantly lower than that of other surfactants. In particular, polyoxyethylene sorbitan oleate (polysorbate 80) showed excellent results, and its cytotoxicity was about 1/1000th that of the surfactants constituting commercially available shampoos (Table 1). The cytotoxicity of the sorbes was about 1/100 that of the surfactants constituting commercially available shampoos (Table 1). Surfactants other than sorbes and polysorbates showed similar strong cytotoxicity. Note that this result was similar even when human epidermal keratinocytes were used.

Next, the low cytotoxicity of sorbes and polysorbates will be explained in more detail.
The data in Table 1 suggest a relationship between surfactant structure and cytotoxicity. A surfactant is a combination of a lipophilic group (hydrophobic group) and a hydrophilic group. Lipophilic groups are often composed of alkyl groups of fatty acids. Hydrophilic groups include carboxylic acids, amino acids, sulfonic acids, amines, sugar chains, etc., and provide a wide variety of surfactants. Many surfactants have a lipophilic group and a hydrophilic group linked in a linear chain, and surfactants with these structures showed almost the same strong cytotoxicity regardless of the type of hydrophilic group. Therefore, it is expected that the main cause of cytotoxicity is the alkyl group on the straight chain. This is because the cytotoxicity of these surfactants is approximately the same as that of free fatty acids (Na or K salts).

In fact, the present inventors have discovered that oleic acid or its derivatives bind to cell membranes and exhibit strong cytotoxicity. It has been observed that cytotoxicity is due to disruption of physiological functions when surfactant concentrations are low, and due to destruction of cell membranes when surfactant concentrations are high. As mentioned above, among polysorbates, why is polysorbate 80 particularly low in cytotoxicity?

In the case of polysorbate 80, four large hydrophilic groups are coordinated radially outward, one of which is bound to oleic acid. Therefore, it is presumed that the alkyl group cannot adhere closely to the cell membrane due to steric hindrance and, as a result, does not exhibit cytotoxicity. Alternatively, the large hydrophilic groups may simply impede cell adhesion. Polysorbates are highly hydrophilic and have a low critical micelle concentration, which also seems to be related to their low cytotoxicity. As described below, there was no significant difference in cleaning ability between highly cytotoxic surfactants and sorbes and polysorbates. Although polysorbates have slightly inferior foaming properties, it has been found that they can be the main component of low-toxicity hair washes.

Although sorbes and polysorbates are conventionally known surfactants with excellent safety, they have not been used as main components of cleaning agents for the human body. The reason for this is that it has traditionally been thought that the better the foaming, the better the cleaning performance, and since polysorbates are somewhat inferior in foaming performance, they cannot provide the cleaning performance required for human body detergents. It is assumed that this is because it was considered. This problem will be discussed in more detail below, taking as an example a shampoo containing the low toxicity human body cleansing agent of the present invention.

Next, the low toxicity human body cleaning liquid of the present invention will be explained.
The low-toxicity human body cleansing liquid of the present invention contains the low-toxicity human body cleansing agent as a main ingredient, and contains one or more of the sorbes, the sorbes, and the like as the main ingredients of the surfactant. It contains one or more of the above-mentioned polysorbates as a main component, has the cleaning ability necessary for cleaning the human body, and is excellent in safety. The low toxicity human body cleaning liquid may be an aqueous liquid or an oily liquid. Here, the aqueous liquid refers to water or a mixture of water and a water-soluble solvent. Moreover, an oily liquid refers to a liquid containing oil. In the case of oil-based liquids containing water, either an oil-in-water (O/W type) emulsion in which oil droplets are dispersed in water or a water-in-oil (W/O type) emulsion in which water droplets are dispersed in oil. You can also take For example, an aqueous shampoo can stably disperse oil, and an oil-liquid cleanser can stably disperse water. The critical micelle concentration (CMC) of polysorbate 80 and polysorbate 20 is low, so the surfactant potency is high. In addition, the hydrophilic-lipophilic balance (HLB value), which indicates the relative strength of hydrophilicity and lipophilicity, is large, so the strength of hydrophilicity is high and it is easy to form oil-in-water (O/W type) emulsions. .

Specifically, the low toxicity human body cleaning liquid of the present invention is suitably used as shampoo, body soap, facial soap, cleansing agent, or the like. Hereinafter, the low toxicity human body cleaning liquid will be explained using a typical shampoo as an example. However, the low toxicity human body cleansing liquid of the present invention is not limited to shampoo.

The shampoo of the present invention contains the low toxicity human body cleansing agent (surfactant) as a main ingredient. Specifically, the low toxicity human body cleansing agent comprises the polyoxyethylene sorbitol fatty acid ester (sorbes such as Sorbes 30, Sorbes 40, and Sorbes 60), or the sorbes and the polyoxyethylene sorbitan fatty acid ester (sorbes). The main component of the surfactant is a mixture with polysorbates such as polysorbate 20, polysorbate 60, polysorbate 65, and polysorbate 80.

As used herein, the main component in the ingredients of the low-toxicity human body cleaning liquid specifically refers to a component that is contained in 30% by mass or more of the total ingredients of the low-toxicity human body cleaning liquid, preferably 40% by mass or more. , more preferably 45% by mass or more, still more preferably 50% by mass or more. Note that the compounded components refer to surfactants, treatment components, etc. that are blended in a dispersion medium such as water or oil, and are components excluding the dispersion medium.

The total content of sorbes derived from the low toxicity human body cleansing agent (first embodiment), or the total content of sorbes and polysorbates (second embodiment), which can be contained in the low toxicity shampoo of the present invention. Embodiment) is preferably 0.1 to 80% by mass of the entire cleaning liquid as a dry solid content, taking into account the safety to the scalp and the effect of promoting hair growth. The lower limit is more preferably 0.5% by mass, still more preferably 1% by mass, 2% by mass, particularly preferably 3% by mass. The upper limit is more preferably 50% by mass, still more preferably 30% by mass, 20% by mass, particularly preferably 15% by mass.

In addition, the total content of sorbes (first embodiment) or the total content of sorbes and polysorbates (second embodiment) in the total of all components contained in a low-toxicity human cleaning liquid such as shampoo ) is 30% by mass, more preferably 40% by mass or more, more preferably 45% by mass or more, particularly preferably 50% by mass or more. In addition, the upper limit is approximately 90% by mass, preferably 80% by mass, and more preferably is 70% by mass, more preferably 60% by mass.

Although shampoos containing the sorbes and polysorbates have extremely low toxicity, sorbes and polysorbates have not been used as cleansing ingredients in shampoos in the past. A possible reason for this is that sorbes and polysorbates have poor foaming properties (foaming properties).
However, as will be described later, the results of the research conducted by the present inventors show that sorbes and polysorbates have inferior foaming properties compared to general surfactants, and do not have the sufficient cleansing properties required for shampoos. It turned out that I have it. This is because while foaming is a phenomenon that occurs at the interface between the aqueous and gas phases, detergency is a phenomenon that occurs at the interface between the aqueous and solid phases, so detergency has no significant relationship with foaming. It can be considered that this is because Although sorbes and polysorbates have poor foaming properties, they have extremely low cytotoxicity and sufficient detergency, which are characteristics first discovered by the present inventors.

Next, the foaming properties (quality of foaming) of the shampoo using the polysorbates of the present invention will be explained in detail.
The present inventors conducted foaming tests using wigs (hair attachments) for many surfactants. As a result, the foaming properties of polysorbates were significantly lower than those of highly cytotoxic surfactants. The foaming properties of the polysorbates were in the order of polysorbate 80>polysorbate 20>polysorbate 60. There was almost no difference in the foaming properties of the sorbes among Sorbes 30, Sorbes 40, and Sorbes 60.

The foaming properties of surfactants result from lowering the surface tension of aqueous solutions. Foaming depends on the stability of the interface between the gas and water phases. The hydrophobic groups of the surfactant line up on the gas phase surface, and the hydrophilic groups line up on the water phase side. Therefore, the linear surfactants are regularly arranged in tandem on the interface, increasing the stability of the foam. Additionally, if the hydrophilic groups are electrically charged, they will repel each other, increasing the stability of the foam. Sorbetes and polysorbates are nonionic, and large hydrophilic groups are expected to prevent tight tandem formation. Among the polysorbates, polysorbate 80 to which oleic acid was bonded had the best foaming properties, and polysorbate 60 to which stearic acid was bonded was the worst. It has been reported that foaming depends on the length of the alkyl group of the fatty acid, but oleic acid and stearic acid have the same length. Oleic acid is an unsaturated fatty acid that contains one double bond and is bent into a cis form, and stearic acid is a saturated fatty acid with a straight chain. It is interesting that this difference greatly affected foaming. Since polysorbate 65 has three stearic acids bound together, it has low solubility in water and low foaming. As a result, the foaming properties of polysorbates were significantly lower than those of highly cytotoxic surfactants. The foaming properties of the polysorbates were in the order of polysorbate 80>polysorbate 20>polysorbate 60. There was almost no difference in the foaming properties of the sorbes among Sorbes 30, Sorbes 40, and Sorbes 60. It is suggested that the average degree of polymerization of ethylene oxide does not affect foaming properties.

The ID50 of the low toxicity human body cleansing liquid such as shampoo of the present invention is preferably 2000 μg/mL or more, more preferably 5000 μg/mL or more, and even more preferably 10000 μg/mL or more. Shampoos and the like having an ID50 in this range have low cytotoxicity and will not cause thinning hair or hair loss even if used in excess.

Next, the ingredients and toxicity of conventional shampoos investigated by the present inventors will be explained in detail.

Shampoos currently on the market contain a variety of surfactants as shown in the general classification in Table 2.

The present inventors systematically investigated the composition (ion type and content) of surfactant components contained in common shampoos. The results are shown in Table 3.

In Table 3, "A1 to A4" on the horizontal axis indicates the type of shampoo for oily hair, "B1, B2" on the horizontal axis indicates the type of baby shampoo, and "C1 to C4" on the horizontal axis indicates the type of regular shampoo. , "D1 to D9" on the horizontal axis represent the types of mild shampoo, respectively.
Also, "AN1 to AN5" on the vertical axis indicates the type of anionic surfactant, "NI6 to NI14" on the vertical axis indicates the type of nonionic surfactant, and "CAT15, CAT16" indicates the type of cationic surfactant. "AM17 to AM19" on the vertical axis represent the types of amphoteric surfactants, respectively.

From Table 3, it was found that one shampoo contained a plurality of surfactants, and that their total amount was approximately 10 to 15% by mass. However, there is no data that accurately measures the cytotoxicity of shampoos, including shampoos that have been evaluated as relatively safe. Furthermore, the cytotoxicity of surfactants contained in shampoos has not been measured. Therefore, in order to provide safe shampoos, it is essential to comprehensively evaluate the cytotoxicity of shampoos and surfactants. Therefore, the present inventors purchased more than 10 shampoos that have been evaluated as being relatively safe in Japan, and investigated the surfactant components they contained. Table 4 shows surfactants contained in commercially available shampoos. The cytotoxicity (ID50) of these surfactants was investigated. The results are shown in Table 1.
In addition, the cytotoxicity (ID50) of the treatment ingredients, moisturizers, peptides, protein decomposition products, coating ingredients, positively charged sugars, plant extracts, etc. contained therein was investigated. The results are shown in Table 1.

Furthermore, detailed cytotoxicity tests were comprehensively conducted on these shampoo components. The cytotoxicity test was conducted because it is known that the toxicity of surfactants and the like to living organisms can be replaced by a toxicity test at the cellular level (Non-Patent Document 1). Toxicity tests using cells have the advantage of being simple, highly accurate, and elucidating the mechanism of action.

The present inventors investigated the cytotoxicity of commercially available shampoos (Table 4) on human normal fibroblast cells using the method described in the Examples. That is, for the evaluation of cytotoxicity, the concentration (ID50) that kills 50% of cells after 30 minutes of treatment was used. The results are shown in Table 5. All shampoos showed similar significant cytotoxicity after only 30 minutes of contact with cells (Table 5). From Table 5, the concentration (ID50) that killed 50% of the cells was approximately 500 to 1000 μg/ml (0.05 to 0.1% by mass). In other words, if shampoo diluted 1 to 2000 times is administered to cells for 30 minutes, 50% of the cells will die.

From the results in Table 5, it was found that significant cytotoxicity was unavoidable in both cases, when a portion of the shampoo was applied to the wet scalp, or when diluted with warm water and applied to the head. . If high concentrations of surfactant enter the hair follicle, it is predicted that the toxicity to hair root cells could persist for a longer period of time. Generally, shampoo contains 10 to 15% by mass (10 to 15 x 10 ^-2 g/ml) of surfactant, so it is expected that the cytotoxicity of surfactant is 6 to 10 times stronger than that of shampoo. . Therefore, in order to provide a shampoo with low cytotoxicity, it is necessary to find a new surfactant with sufficiently low cytotoxicity. At the same time, it is also essential to use treatment ingredients or auxiliary ingredients that have low cytotoxicity.

Next, various auxiliary ingredients added to low-toxicity human body cleansing liquids such as shampoos will be explained.
The shampoo of the present invention contains the above-mentioned low toxicity human body cleansing agent, and the shampoo further contains sorbes or a mixture of sorbes and polysorbates to improve the mass of foam. In addition, one or more other surfactants can be added as auxiliary ingredients. Specifically, amino acid surfactants (cocoyl glutamate disodium, cocoyl glutamate K, cocoyl glutamate TEA, cocoyl alanine TEA, lauroyl methyl alanine Na, cocoyl methyl alanine Na, cocoyl methyl taurate Na, lauroyl sarcosine Na, sulfosuccinic acid (c12 -14) Palace 2-Na, dilauroylglutamate lysine Na, lauroyl aspartate Na, cocoyl arginine ethyl PCA, etc.), betaine surfactants (cocamidopropyl betaine, lauramide propyl betaine, lauryl betaine), sulfonic acid interfaces Activator (olefin (C14-16) sodium sulfonate), higher alcohol surfactant (sodium lauryl sulfate, sodium laureth sulfate, sodium laureth-4 carboxylate, sodium cocoamphopropionate), amine surfactant (sodium sulfonate), aramidopropyl dimethylamine, behentrimonium methosulfate, cetearamid ethyl diethonium hydrolyzed rice protein, cete aramide ethyl diethonium succinoyl hydrolyzed pea protein), nonionic surfactants (decyl glucoside, cocamide DEA, lauramide DEA, lauryl glucoside) ), etc., peptide surfactants (surfactin Na). Among these auxiliary ingredients, it is preferable to use sodium lauroyl aspartate, sodium dilauroylglutamate lysine, cocamidopropyl betaine, cocamide DEA, and surfactin Na, which have relatively low cytotoxicity.

The total content of the surfactant as the auxiliary cleaning component is preferably 0.1 to 10% by mass as dry solid content. If the content is too low, the effect of improving the mass of foam may not be achieved. If the content is too large, cytotoxicity may become strong. From this point of view, the lower limit is more preferably 0.3% by mass, still more preferably 0.5% by mass, and particularly preferably 0.7% by mass. Further, the upper limit thereof is more preferably 8% by mass, still more preferably 7% by mass, 6% by mass, 5% by mass, or 4.5% by mass, and particularly preferably 3% by mass.

The low-toxicity shampoo of the present invention preferably contains one or more of a moisturizing agent, a hair improving agent, or a scalp protecting agent as a treatment component. The treatment component has the effect of moisturizing the scalp and hair, reducing the toxicity of chemical components, repairing hair damage, improving the firmness and stiffness of the hair, and adding humidity and a moist feeling to the hair.

Specifically, the treatment ingredients include various surfactants (cocoyl arginine ethyl PCA, N-lauroyl-L-glutamate di(phytosteryl 2-octyldodecyl), dilauroylglutamate lysine Na, lauroylglutamate dioctyldodeceth-5, Alkyl (C12,14) oxyhydroxypropyl arginine HCl, cocoyl arginine ethyl PCA, etc.), yogurt, amino acids/proteins (keratin, hydrolyzed keratin, hydrolyzed silk, hydrolyzed casein, hydrolyzed collagen, hydrolyzed wheat, hydrolyzed (soy protein, glutamic acid, arginine, sodium aspartate, glycine, etc.), plant extracts, ceramides, hydroxypropyltrimonium, hydroxyethyl urea, platinum nanocolloid, various ceramides, honey, brown algae extract, green algae extract, red algae extract, Caliphylla noricis, ectoine, γ-docosalactone, betaine, bentonite, trehalose, ceramide 3, Laminaria ochloroica extract, hydrolyzed sesame protein PG propylmethylsilanediol, rice extract, rice bran extract, meadowfoam-δ-lactone), amo Examples include dimethicone, stearamidopropyldimethylamine, behentrimonium methosulfate, and the like.
In addition, treatment ingredients that protect the hair cuticle (cetearamide ethyldiethonium hydrolyzed rice protein, cetearamidethyldiethonium succinoyl hydrolyzed pea protein, avocado oil, jojoba oil, olive oil, vegetable oils, lanolin, palmitic acid) Ethylhexyl, lanolin derivatives, isopropyl myristate, squalane, petrolatum, fatty acid amides, ceramide, mineral oil, glyceryl oleate, cetanol, octyldodecanol, hydrogenated pentaerythrityl rosinate, isopentyl diol, cationized cellulose, hydroxyethyl cellulose , chitosan, octyldodecyl isostearate, alkyl benzoate (C12-15), 18-methyleicosanoic acid (+ stearoxypropyl dimethylamine), almond oil, jojoba oil, argania spinosa kernel oil, camellia oil, isoamyl laurate , octyl methoxycinnamate, soybean sterol, baobab seed oil, prune seed extract, safflower oil, lupine seed oil, mango seed oil, theobromagrange florum seed oil, carapaguaianensis seed oil), vegetable oil, synthetic oil, etc. (Avocado oil, rice germ oil, hybrid sunflower oil, sclerocariabirea seed oil, jojoba seed oil, triethylhexinone, squalane, triethylhexanoin, hydrogenated polyisobutene, rice germ oil, shea butter, octyldodecyl myristate, Yucha oil, walnut seed oil, rice bran oil fatty acid phytosteryl, ethylhexyl methoxycinnamate, candelilla wax, microcrystalline wax, canine crismoid extract), silicones (dimethicone, cyclomethicone, cationized polymers), polyquaternium-11 , Polyquaternium-55, Polyquaternium-7, Lipidure (Polyquaternium-64, etc.), UV absorbers (1.4-tert-butyl-4'-methoxydibenzoylmethane (t-butylmethoxydibenzoylmethane), 2-ethylhexyl para-methoxycinnamate (such as ethylhexyl methoxycinnamate).
In addition, 2-hydroxy-4-methoxybenzophenone (oxybenzone-3), PABA oxybenzones, PABA ethyl, amyldimethyl PABA, isopropyl ethyl cinnamate, esculin, ethylhexyl triazone, octyldimethoxycinnamate, glyceryl octoate, octyl triazone. , octocrylene, oryzanol, ethyl guaiazulene sulfonate, glyceryl PABA, isocetyl salicylate, octyl salicylate, glycol salicylate, phenyl salicylate, ethyl diisopropyl cinnamate, methyl diisopropyl cinnamate, distyrylbiphenyl disulfonthane 2Na, cinoxate, dimethoxybenzylidene dioxoimidazolidine , dimethyl PABA, dimorpholinopyridazinone, diphenylcarbomethoxyacetoxynaphthopyran, spirulina platensis, terephthalylidene dicanfursulfonic acid, drometrizole, drometrizole trisiloxane, methylbis(trimethylsiloxy)silyliso trimethoxycinnamate Pentyl, tocotrienol, diethylhexyl naphthalene dicarboxylate, isopropyl paramethoxycinnamate, bisethylhexyloxyphenol methoxyphenyl triazine, phenylbenzimidazole sulfonic acid, ferulic acid, phenylbenzimidazole sulfonic acid, bumetrizole, octyl propionate, benzotriazole Ludodecyl p-cresol, benzotriazolylbutylphenol sulfonic acid Na, homosalate, octyl methoxycinnamate, methylbenzylidene camphor, methylenebisbenzotriazolyltetramethylbutylphenol, ethylhexyl methoxycinnamate, diethylaminohydroxybenzoylbenzoate hexyl, succinic acid (diethylhexyl) etc. are mentioned as treatment ingredients.

The total content of treatment components that can be contained in the shampoo of the present invention is preferably 0.1 to 90% by mass as dry solid content, taking into account safety to the scalp and hair growth promoting effect. The lower limit is more preferably 1% by mass, still more preferably 2% by mass, and particularly preferably 3% by mass. Further, the upper limit thereof is more preferably 50% by mass, still more preferably 30% by mass, 20% by mass, or 10% by mass, particularly preferably 7% by mass.

The shampoo of the invention can contain herbal extracts that activate hair follicles and scalp cells. The herbs are obtained from amla, clownflower, hawkweed, centella asiatica, Indian pine, chiretta asiatica, bellflower, thorns baleria, St. japonica, Ceylon daylily, licorice, lily pad, lily pad, water lily, sandalwood, staghorn balan, syringa, and aloe vera. One or more extracts may be combined simultaneously. Risilicon extract, royal jelly extract, persimmon tannin, Roman chamomile flower extract/rosemary extract, Calendula extract, chickpea seed extract, arnica flower extract, dead nettle flower extract, button extract, placenta extract/Furilia flower extract, Jasperum extract/St. Extracts: Pinus cone extract, garlic extract, burdock root extract, gentian extract, mugwort extract, chamomile extract, mustard extract, dead nettle flower extract, Panax ginseng extract, okra extract, St. lucidum leaf extract, yuzu extract, tocopherol Gagome extract, hyaluronic acid Na, poly-γ-glutamic acid Na, cysteine/oligomeric proanthocyanidins, purple root extract, turmeric rhizome extract, menthol, Japanese cabbage extract, Panax ginseng root extract, ginger rhizome extract, aloe vera leaf extract, capsicum fruit extract, honorite, vanillyl butyl, aloe vera Leaf extract, hibiscus flower extract, mustard extract, burdock extract, Ivy extract, garlic extract, hydrolyzed chickpea seed extract, tocopherol, arnica flower extract, dead nettle flower extract, peony extract, placenta extract/mundium flower extract, Japanese commonweed extract - Examples include pine extract, rosemary extract, and Roman chamomile extract.

The total content of herbs that can be contained in the hair wash of the present invention is preferably 0.01 to 50% by mass as dry solid content, more preferably 0.01 to 50% by mass, taking into account safety to the scalp and hair growth promoting effect. is 0.1 to 10% by mass.

The term "herb" as used herein refers to useful plants collected in the Indian subcontinent, the Middle East, Southeast Asia, etc. or a mixture of multiple parts or the whole plant). The production area of the above-mentioned plants that characterize the present invention is not particularly limited. In either case, one or a mixture of parts of the plant such as leaves, stems, trunks, bark, young buds, flowers, fruits, seeds, roots, etc., or extracts from the whole plant can be used.

When obtaining an extract from a plant, each part may be used raw, but it may be necessary to perform appropriate pretreatment such as drying, shredding, crushing, squeezing, or fermentation before using a solvent at low temperature or heating. Extract. The extraction method is not particularly limited, but includes, for example, a method of immersing one part or two or more parts of the plant in a solvent at low temperature or at room temperature to heating. The extraction time is set depending on the type of extraction solvent and the extraction temperature, but is preferably about 1 hour to 2 weeks. Extraction solvents include, for example, water, lower monohydric alcohols (methyl alcohol, ethyl alcohol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, etc.), liquid polyhydric alcohols (glycerin, propylene glycol, dipropylene glycol, etc.). , 1,3-butylene glycol, etc.), lower esters (ethyl acetate, butyl acetate, etc.), hydrocarbons (benzene, hexane, pentane, etc.), ketones (acetone, methyl ethyl ketone, etc.), ethers (diethyl ether, tetrahydrofuran, dihydrofuran, etc.) (propyl ether, etc.), acetonitrile, etc., and one or more types thereof can be used. Alternatively, vegetable oils (sesame oil, coconut oil, olive oil, etc.), physiological saline, phosphate buffer, phosphate buffered saline, etc. may be used. If necessary, purification treatments such as deodorization and decolorization may be performed within a range that does not impair the effects of the present invention. Furthermore, if necessary, after adding a preservative and a fungicide (phenoxyethanol, paraoxybenzoic acid ester, etc.), the product may be stored at a low temperature for 1 to 2 days and then filtered.

As an example of a preferred method for extracting plants that characterizes the present invention, extraction is carried out at room temperature or heated for 1 to 10 days using aqueous ethyl alcohol or 1,3-butylene glycol at a concentration of 0 to 100% by volume. An example of this is to filter it afterwards. An example of a method is to leave the obtained filtrate at a low temperature to room temperature for about one week to age it, and then filter it again.

Hair growth/hair nourishment auxiliary ingredients can be added to the low toxicity shampoo of the present invention. As hair growth/hair nourishment auxiliary ingredients, for example, cephalanthine, γ-oryzanol, carpronium chloride, acetylcholine, capsicum tincture, cantharis tincture, ginger tincture, nonylic acid vanylamide, salicylic acid, resorcinol, lactic acid, placenta extract, pentadecanoic acid glyceride, hinokitiol. , allantoin, glycyrrhizic acid, glycyrrhetinic acid, isopropyl methylphenol, triclosan, zinc pyrithione, hinokitiol, menthol, camphor, photosensor No. 301, Cordyceps sinensis extract, trans-3,4,-dimethyl-3-hydroxyflavanone, Hypericum perforatum extract, Netherlands Mustard extract, Clara extract, wheat germ extract, Japanese pepper extract, and other female hormones can also be added.

Hair moisturizing ingredients can be added to the low toxicity shampoo of the present invention. Examples of hair moisturizing ingredients include alginic acid, sodium alginate, xylitol, glucose, polyethylene glycol, propylene glycol, dipropylene glycol, glycerin, polyglycerin, 1,3-butylene glycol, 1,2-pentanediol, hexylene glycol, xylitol, Sorbitol, POE methyl glucoside, maltitol, maltose, mannitol, lysine, honey, royal jelly, chondroitin sulfate, sodium chondroitin sulfate, hyaluronic acid, sodium hyaluronate, sodium acetyl hyaluronate, mucoitin sulfate, caronic acid, tranexamic acid, betaine, trehalose , chitosan, urea, ceramide, atelocollagen, cholesteryl-12-hydroxystearate, sodium lactate, bile salts, dl-pyrrolidone carboxylic acid salt, soluble collagen, diglycerin (EO) PO adduct, Acetabella extract, Asparagus extract A substance such as a rose root extract, a quince seed extract, a guava leaf extract, a yarrow extract, a melilot extract, etc. can be added.

For example, amino acids, nucleic acid precursors, and vitamins can be added to the low-toxicity shampoo of the present invention as hair nourishing ingredients. Amino acids refer to 20 essential and non-essential amino acids. Nucleic acid precursors refer to adenine, guanine, cytosine, uracil, thymine, and their ribose and 2-deoxyribose forms. Vitamins refer to 13 types of vitamins A, B1, B2, B6, B12, C, D, E, K, folic acid, niacin, biotin, and pantothenic acid, or derivatives thereof. It may be a mixture of these or a partial mixture thereof. Further, yeast or plant extracts may be used as the supply source.

For the low toxicity shampoo of the present invention, antioxidant ingredients include, for example, astaxanthin, β-carotene, γ-oryzanol, kinetin, tocopherol, dibutylhydroxytoluene, flavonoids, SOD, catalase, fullerene, phytic acid, ferulic acid, Chlorogenic acid, propyl gallate, green tea extract, rosemary extract, rosehip extract, calamus extract, horsetail extract, hamamelis extract, parsley extract, loquat leaf extract, grapefruit extract, meadowsweet extract, Lychee extract, mugwort extract, peach leaf extract, mango extract, botanpi extract, pine bark extract, platinum, ubiquinone, α-lipoic acid, etc. can be added.

For the low-toxicity shampoo of the present invention, the blood circulation-promoting ingredients include, for example, Japanese salamander extract, ginger extract, nebula extract, chimpi extract, chili pepper extract, Japanese acanthus extract, peony extract, and nonylic acid. Valenilamide, nicotinic acid benzyl ester, nicotinic acid β-butoxyethyl ester, capsaicin, canthalys tincture, ictamol, caffeine, tannic acid, α-borneol, tocopherol nicotinate, inositol hexanicotinate, acetylcholine, cephalanthine, γ-oryzanol, etc. , can be added.

For the low toxicity shampoo of the present invention, anti-inflammatory ingredients such as aminocaproic acid, allantoin, indomethacin, bisabolol, saponin, lysotium chloride, azulene, guaiazulene, guaiazulene sulfonate, glycyrrhizic acid and its derivatives, glycyrrhetinic acid and Derivatives thereof, salicylic acid and derivatives thereof, hinokitiol, photosensitizers, tranexamic acid and derivatives thereof, zinc oxide, turmeric extract, genus shoko extract, peony extract, reishi extract, orchid extract, etc. can be added.

In addition to the above-mentioned ingredients, the low-toxicity shampoo of the present invention may include oils and fats, waxes, hydrocarbons, fatty acids, and other ingredients commonly used in external preparations, within a range that does not impair the effects of the present invention. Alcohols, esters, water-soluble polymers, surfactants, metal soaps, alcohols, polyhydric alcohols, pH adjusters, preservatives, fragrances, powders, thickeners, pigments, chelating agents, etc. are blended as appropriate. be able to.

In addition to the above-mentioned components, it is desirable that the low-toxicity shampoo of the present invention contains salts at the same time. Salts include sodium chloride, potassium chloride, sodium phosphate, potassium phosphate, EDTA, silicates, and the like. These salts can stabilize the hair wash or improve the cleaning effect.

The low toxicity human body cleansing agent of the present invention can be applied to cosmetics, quasi-drugs, and pharmaceuticals. Specifically, as described above, it can be used as a low-toxic human body cleaning liquid, and can be used in shampoos, as well as body soaps, facial soaps, and cleansers. Furthermore, the low toxicity human body cleansing agent can be used for, for example, hair growth/hair tonic, hair tonic, hair liquid, head lotion, head emulsion, head cream, head mousse, and eyebrow beauty. It can be used for liquids, eyelash serums, rinses, hair treatments, etc., as well as low viscosity liquids, pastes, creams, foams, body emulsions, packs, ointments, powders, aerosols, patches, etc., hair growth/hair nourishing agents, and hair treatments. It can be applied to tonics, hair liquids, head lotions, head emulsions, head creams, head mousses, eyebrow serums, eyelash serums, rinses, hair treatments, etc.

The low toxicity human body cleansing agent that characterizes the present invention was born out of the inventors' long years of basic research into cell aging. Through systematic surfactant toxicity testing, we demonstrated for the first time that most surfactants have strong cytotoxicity, but that this is not the case for surfactants with special structures. This is the background from which the present invention was born. The cleaning agent according to the present invention far exceeds existing similar products in terms of safety, and its superiority and usefulness in the medical and beauty fields are obvious. The present invention is good news for those who suffer from transdermal toxicity from detergents and those who suffer from hair loss.

Next, the low toxicity human body cleansing agent and low toxicity shampoo of the present invention will be explained in more detail with reference to Examples. However, the present invention is not limited to the examples at all.

Examples 1 to 4
As surfactants, (Example 1) Solves 30, (Example 2) Solves 40, (Example 3) Solves 60 were each dissolved in an aqueous solution of 10 g/100 mL, and (Example 4) Solves 40/ Polysorbate 60 3.5g/6.5g/100mL, (Example 5) Sorbes 40/Polysorbate 60 5g/5g/100mL, (Example 6) Sorbes 40/Polysorbate 60 6.5g/3.5g/100mL An aqueous solution was prepared.

The resulting aqueous solution was subjected to a cytotoxicity test using the method described below. As shown in Table 1, the results of the cytotoxicity test were as follows: The aqueous solution of Example 1 (Sorbes 30) had an ID50 of 5000 μg/mL or more, the aqueous solution of Example 2 (Sorbes 40) had an ID50 of 10000 to 20000 μg/mL, and ID50 of the aqueous solution of Example 3 (Sorbes 60) is 10,000 to 20,000 μg/mL, ID50 of the aqueous solution of Example 4 (mixture of Sorbes 40 and Polysorbate 60 (weight ratio 25/75)) is 10,000 to 20,000 μg/mL, Example 5 The ID50 of the aqueous solution of Example 6 (mixture of Sorbeth 40 and Polysorbate 60 (weight ratio 50/50)) is 10000 to 20000 μg/mL, and the ID50 of the aqueous solution of Example 6 (mixture of Sorbeth 40 and Polysorbate 60 (weight ratio 75/25)) was 10,000 to 20,000 μg/mL.

<Cytotoxicity test>
Each aqueous solution prepared as described above and a commercially available shampoo (comparative example) were evaluated for their growth inhibiting effects on skin fibroblasts and skin keratinocytes. The results are shown in Table 1 above for Examples 1 to 6, and in Table 5 above for the commercially available shampoo (comparative example).
Note that there was no significant difference in the results using skin fibroblasts and skin keratinocytes. Therefore, in this specification, the results using skin fibroblasts are shown in Table 1 above for the aqueous solutions of Examples 1 to 6, and Table 5 for the commercially available shampoo (comparative example).

The cytotoxicity test was conducted in the following manner.
1 x 10 ⁴ facial skin fibroblasts (purchased from Toyobo) were seeded in a poly-L-lysine coated dish (60 mm petri dish), and incubated in DMEM medium containing 5% fetal bovine serum in the presence of 5% carbon dioxide. The cells were cultured at 37°C. The next day, appropriately diluted samples were added. After 30 minutes of addition, the medium was sucked out, washed twice with normal medium, and culture was continued with normal medium. Note that the medium was replaced every 3 days, and cell morphology was observed one week later. Next, the formed cell colonies were stained with methylene blue, and the number and size of the colonies were measured. The cell growth inhibition rate of the sample was determined as follows. The number of colonies in the additive-free group was set as 100%. The number of colonies in the sample-added group was counted, and the colony formation rate (%) relative to the non-additive group was calculated. A cell growth inhibition curve in which the horizontal axis represents the sample concentration and the vertical axis represents the colony formation rate (%) was prepared, and the concentration ID50 (μg/mL) that inhibited colony formation by 50% was determined.

Evaluation of cytotoxicity According to Tables 1 and 5, the cytotoxicity of the aqueous solution of the low toxicity human body cleansing agent of the present invention is approximately one-tenth that of commercially available shampoo components and commercially available shampoos. I understand that.

<Cleaning test>
The aqueous solution of Example 1 (Sorbes 30), the aqueous solution of Example 2 (Sorbes 40), the aqueous solution of Example 3 (Sorbes 60), the aqueous solution of Example 4 (Sorbes 40/Polysorbate 60 (weight ratio As a comparative example, A cleaning test was conducted on various surfactants constituting conventional shampoos using the apparatus shown in FIG. The surfactant component used as a comparative example is one commonly used in shampoos. The detergency was expressed as the concentration that completely washed away the oil and fat applied to the slide glass in 2 minutes. The results are shown in Table 6.

The cleaning test was conducted as follows.
(Example 1) Sorbes 30, (Example 2) Sorbes 40, (Example 3) Sorbes 60, (Example 4) Sorbes 40/Polysorbate 60 (weight ratio 25/75), (Example 4) Sorbes 40/Polysorbate 60 (weight ratio 25/75), prepared as described above. Example 5) Sorbeth 40/Polysorbate 60 (weight ratio 50/50), (Example 6) Sorbeth 40/Polysorbate 60 (weight ratio 75/25), various surfactants constituting conventional shampoos, commercially available shampoos A cleaning test was conducted using the apparatus shown in FIG. As a comparison group, a surfactant component often used in shampoos and a commercially available shampoo were used. The detergency was expressed as the concentration that completely washed away the oil and fat applied to the slide glass in 2 minutes.

As shown in Table 6, the detergency of the aqueous solution of Example 1 (Solves 30) is 20 μg/mL, the detergency of the aqueous solution of Example 2 (Solves 40) is 20 μg/mL, and the aqueous solution of Example 3 (Solves 60). The detergency of the aqueous solution of Example 4 (mixture of Solves 40 and Polysorbate 60 (weight ratio 25/75)) is 20-40, and the detergency of the aqueous solution of Example 5 (Mixture of Sorbes 40 and Polysorbate 60 (weight ratio 25/75)) is 20 μg / mL. (weight ratio 50/50)) has a cleaning power of 20 to 40
The detergency of the shampoo of Example 6 (a mixture of Sorbes 40 and Polysorbate 60 (weight ratio 75/25) was 20.

Examples 7 and 8
As Example 7, a foaming agent, a base material, and a preservative were added to the aqueous solution of Example 2 to create a shampoo, and as Example 8, a foaming agent, a base material, and a preservative were added to the aqueous solution of Example 2. , created a shampoo. Table 7 shows the formulation of each shampoo.

Cytotoxicity tests and washing tests were conducted in the same manner as in Examples 1 to 6. The results of the cytotoxicity test were 10,000 μg/mL in Example 7 and 10,000 μg/mL in Example 8. The results of the cleaning test were 20 μg/mL in Example 7 and 20 μg/mL in Example 8.

From Table 6 and the cleaning test results of Examples 7 and 8 above, it is clear that surfactants made of sorbes, mixtures of sorbes and polysorbates, and the prototype shampoos (Examples 7 and 8) were not used with other surfactants. It can be seen that it has a cleaning performance that is comparable to that of detergents and shampoos.

[Figure 1]
Number 1: Sorbes 30
Number 2: Sorbes 40
Number 3: Sorbes 60

[Figure 2]
Number 1: Polysorbate 20
Number 2: Polysorbate 60
Number 3: Polysorbate 80

[Figure 3]
Number 1: Mixture of Sorbeth 40 and Polysorbate 60 (weight ratio 25/75)
Number 2: Mixture of Sorbeth 40 and Polysorbate 60 (weight ratio 50/50)
Number 3: Mixture of Sorbeth 40 and Polysorbate 60 (weight ratio 75/25)

[Figure 4]
Number 1: Scalp D
Number 2: FNCL amino shampoo
Number 3: CU shampoo
Number 4: Herb Garden Shampoo
Number 5: Herb Garden Conditioner
Number 6: Haru
Number 7: Adjuvant Number 8: Estessimo
Number 9: Ayurbeaute Number 10: ELSEVE

Claims (8)

A low-toxic human body cleansing agent containing a surfactant as a cleaning ingredient,
The surfactant is
A polyoxyethylene sorbitol fatty acid ester represented by the following structural formula (1),
A mixture with polyoxyethylene sorbitan fatty acid ester represented by the following structural formula (2) (including cases where the content of polyoxyethylene sorbitan fatty acid ester is 0 % by mass ) as the main component of the surfactant. It contains 50% by mass or more,
The surfactant has an ID50 (a concentration that kills 50% of cells in 30 minutes) of 10,000 μg /mL or more, and the human body cleansing agent has an ID50 of 10,000 μg/mL or more , and is aqueous and has low toxicity. A low toxicity human body cleansing agent characterized by being used as a hair cleansing agent.


(1) In the formula, at least one of the six X groups is a COR _x group, the remaining X groups are hydrogen, and R _x in the COR _x group is a saturated fatty acid group having 4 to 30 carbon atoms, or a carbon It has 16 to 24 unsaturated fatty acid groups.
Further, the average of the total number of ethylene oxide groups (a+b+c+d+e+f) condensed to sorbitol is within the range of 10 to 150.

(2) In the formula, any one of R ₁ , R ₂ , and R ₃ is a saturated fatty acid group having 4 to 30 carbon atoms or an unsaturated fatty acid group having 16 to 24 carbon atoms, and the remaining two are hydrogen. , or a saturated fatty acid group having 4 to 30 carbon atoms, or an unsaturated fatty acid group having 16 to 24 carbon atoms. Further, the average of the total number of ethylene oxide groups (x+y+z+w) condensed to the sorbitan fatty acid ester is within the range of 10 to 150.
The polyoxyethylene sorbitol fatty acid ester has a total average of 10 to 150 tetraoleate sorbes ((a+b+c+d+e+f), and any four of the six X groups are oleic acid groups, and the remaining two 2. The low toxicity human body cleansing agent according to claim 1, wherein: is hydrogen.
The polyoxyethylene sorbitan fatty acid ester is polyoxyethylene sorbitan monolaurate (polysorbate 20: R ₁ = lauric acid, R ₂ = H, R ₃ = H),
Polyoxyethylene sorbitan monostearate (polysorbate 60: R ₁ = stearic acid, R ₂ = H, R ₃ = H),
Polyoxyethylene sorbitan tristearate (polysorbate 65: R ₁ = R ₂ = R ₃ = stearic acid or palmitic acid),
Claim 1 or 2, characterized in that it is either polyoxyethylene sorbitan oleate (polysorbate 80: R ₁ = oleic acid, R ₂ = H, R ₃ = H) or a mixture of these polysorbates. A low-toxicity cleaning agent for the human body described in .
A low toxicity human body cleansing liquid containing the low toxicity human body cleansing agent according to any one of claims 1 to 3 as a compounded component,
A polyhydric ester of polyoxyethylene sorbitol and a fatty acid derived from the low-toxicity human body cleansing agent, and a polyoxyethylene sorbitan fatty acid ester (including cases where the content of the polyoxyethylene sorbitan fatty acid ester is 0 % by mass ). ) is 0.1 to 80% by mass as dry solid content,
A low toxicity human body cleansing liquid, characterized in that the ID50 of the low toxicity human body cleansing liquid is 10,000 μg/mL or more, and is used as an aqueous low toxicity shampoo.
5. The low-toxicity human body cleaning liquid according to claim 4, comprising at least one of an anionic surfactant, a cationic surfactant, a nonionic surfactant, or an amphoteric surfactant as an auxiliary cleaning component.
6. The auxiliary cleaning component is one or more components selected from Na lauroyl aspartate, Na dilauroyl glutamate lysine, cocamidopropyl betaine, cocamide DEA, and Na surfactin. Low toxicity human cleaning liquid.
The low toxicity human body cleaning liquid according to claim 5 or 6, wherein the total content of the auxiliary cleaning components is 0.1 to 10% by mass as a dry solid content.
Any one of claims 4 to 7, characterized in that it contains at least one of a hair moisturizing component, a hair treatment component, a hair nourishing component, a scalp moisturizing component, and a scalp nourishing component in a total of 0.1 to 90% by mass as dry solid content. A low-toxicity cleaning liquid for human use as described in .